Trade-off Between Validity and Efficiency of Merging P-Values Under Arbitrary Dependence

Various methods of combining individual p-values into one p-value are widely used in many areas of statistical applications. We say that a combining method is valid for arbitrary dependence (VAD) if it does not require any assumption on the dependence structure of the p-values, whereas it is valid for some dependence (VSD) if it requires some specific, perhaps realistic but unjustifiable, dependence structures. The trade-off between validity and efficiency of these methods is studied via analyzing the choices of critical values under different dependence assumptions. We introduce the notions of independence-comonotonicity balance (IC-balance) and the price for validity. In particular, IC-balanced methods always produce an identical critical value for independent and perfectly positively dependent p-values, a specific type of insensitivity to a family of dependence assumptions. We show that, among two very general classes of merging methods commonly used in practice, the Cauchy combination method and the Simes method are the only IC-balanced ones. Simulation studies and a real data analysis are conducted to analyze the sizes and powers of various combining methods in the presence of weak and strong dependence

Inhibition of protein FAK enhances 5-FU chemosensitivity to gastric carcinoma via p53 signaling pathways

Abstract(#br)The small molecule drug 5-fluorouracil (5-FU) is widely used in the treatment for gastric cancer (GC), however, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, plays a key role in adhesion, migration, and proliferation of gastric carcinoma cells, suggesting that this kinase may be a promising therapeutic target. Differentially expressed FAK in GC tissue was detected by RT-qPCR and TCGA database analysis. To investigate the biological functions of FAK, loss-of-function experiments were performed. CCK-8 assay, colony formation assay, flow cytometry, dual-luciferase reporter assays, and western blot assays were conducted to determine the underlying mechanisms of FAK in 5-FU chemosensitivity in GC. FAK is overexpressed in GC patients, and positively correlated with poor prognosis. The use of shRNA interference to target FAK decreased proliferation and increased apoptosis of GC cells in vitro. Importantly, FAK silencing enhanced the therapeutic efficacy of 5-FU, leading to reduced tumor growth in vivo . We further demonstrated that FAK silencing increased 5-FU-induced caspase-3 activity, and promoted p53 transcriptional activities. Clinical data also has shown that patients with higher levels of FAK had significantly shorter overall survival (OS) and time to first progression (FP) than those with lower levels of FAK. These findings indicate that FAK plays a critical role in 5-FU chemosensitivity in GC, and the use of FAK inhibitors as an adjunct to 5-FU might be an effective strategy for patients who undergo chemotherapy

Measuring the Conditional Luminosity and Stellar Mass Functions of Galaxies by Combining the Dark Energy Spectroscopic Instrument Legacy Imaging Surveys Data Release 9, Survey Validation 3, and Year 1 Data

In this investigation, we leverage the combination of the Dark Energy Spectroscopic Instrument (DESI) Legacy Imaging Surveys Data Release 9, Survey Validation 3, and Year 1 data sets to estimate the conditional luminosity functions and conditional stellar mass functions (CLFs and CSMFs) of galaxies across various halo mass bins and redshift ranges. To support our analysis, we utilize a realistic DESI mock galaxy redshift survey (MGRS) generated from a high-resolution Jiutian simulation. An extended halo-based group finder is applied to both MGRS catalogs and DESI observation. By comparing the r- and z-band luminosity functions (LFs) and stellar mass functions (SMFs) derived using both photometric and spectroscopic data, we quantified the impact of photometric redshift (photo-z) errors on the galaxy LFs and SMFs, especially in the low-redshift bin at the low-luminosity/mass end. By conducting prior evaluations of the group finder using MGRS, we successfully obtain a set of CLF and CSMF measurements from observational data. We find that at low redshift, the faint-end slopes of CLFs and CSMFs below ∼109 h −2 L ⊙ (or h −2 M ⊙) evince a compelling concordance with the subhalo mass functions. After correcting the cosmic variance effect of our local Universe following Chen et al., the faint-end slopes of the LFs/SMFs turn out to also be in good agreement with the slope of the halo mass function

Generation of Trophoblast Stem Cells from Rabbit Embryonic Stem Cells with BMP4

Trophoblast stem (TS) cells are ideal models to investigate trophectoderm differentiation and placental development. Herein, we describe the derivation of rabbit trophoblast stem cells from embryonic stem (ES) cells. Rabbit ES cells generated in our laboratory were induced to differentiate in the presence of BMP4 and TS-like cell colonies were isolated and expanded. These cells expressed the molecular markers of mouse TS cells, were able to invade, give rise to derivatives of TS cells, and chimerize placental tissues when injected into blastocysts. The rabbit TS-like cells maintained self-renewal in culture medium with serum but without growth factors or feeder cells, whilst their proliferation and identity were compromised by inhibitors of FGFs and TGF-β receptors. Taken together, our study demonstrated the derivation of rabbit TS cells and suggested the essential roles of FGF and TGF-β signalings in maintenance of rabbit TS cell self-renewal

Impact of Air Pollution on Short-Term Movements: Evidence from Air Travels in China

10.1093/jeg/lbaa005Journal of Economic Geography420939 - 96

Genome-wide analysis of microRNAs expression profiling in patients with primary IgA nephropathy

The aim of this study was to investigate the differential expression characteristics and the roles of the genome-wide microRNAs (miRNAs) in immunoglobulin A nephropathy (IgAN) kidney tissues. We used Illumina high-throughput sequencing technology to evaluate the miRNAs expression of six biopsy tissues from IgAN and six normal renal cortex specimens from patients with renal cell carcinoma. We observed a total of 85 miRNAs that were differentially expressed in the six IgAN patients, of which 11 miRNAs were up-regulated and 74 miRNAs were down-regulated in patients' tissues compared with control tissues. Additionally, we identified 55 candidate novel miRNAs in our study, which comprised seven candidates who were detected in the IgAN group and 49 candidates who were detected in the control group. Only one candidate (miR-n-9) was expressed in both groups. The bioinformatics showed that the regulated target genes of differentially expressed miRNAs were associated with immune and renal pathological changes. The identification of specific tissue miRNAs in our study not only helped clarify the genetics or immunology mechanisms involved in the pathogenesis of IgAN but also helped explain the pathological changes in the kidney tissues. We hypothesize that some significant miRNAs might potentially serve as novel diagnostic biomarkers in IgAN patients

Geochronology, Whole-Rock Geochemistry, and Sr–Nd–Hf Isotopes of Granitoids in the Tongshanling Ore Field, South China: Insights into Cu and W Metallogenic Specificity

The Qin-Hang Metallogenic Belt (QHMB), an important metallogenic belt in South China, hosts Cu and W–Sn polymetallic deposits. The Tongshanling ore field in the QHMB is characterized by the coexistence of Cu- and W-bearing polymetallic deposits, which are related to granodiorite and granite porphyry. This study examined whole-rock geochemistry, geochronology, and Sr–Nd–Hf isotopes to determine the genetic relationship between diverse ore-related granitoids (i.e., granodiorite and granite porphyry) and Cu–W metallogeny in the Tongshanling ore field. Zircon LA-ICP-MS U–Pb dating shows that the granodiorite and granite porphyry in the Tongshanling ore field were emplaced at 163.7 ± 0.4 Ma to 154.7 ± 0.6 Ma and 161.1 ± 0.3 Ma, respectively. Geochemically, the granodiorites are classified as oxidized I-type, while the highly evolved granite porphyry is reduced A-type. The Lu–Hf isotopic composition of the granodiorites is characterized by εHf(t) values ranging from –10.49 to –4.99 (average = –7.17), with corresponding TDMC ages ranging from 1524 to 1877 Ma (average = 1682 Ma). In contrast, the granite porphyry has higher εHf(t) values (–3.60 to –1.58, average = –2.78) and younger TDMC (1310–1438 Ma, average = 1387 Ma). The εNd(t) values of granodiorite are −8.06 to −7.37 and the two-stage model ages (TDM2) are 1543–1598 Ma, while the granite porphyry has higher εNd(t) values (−3.0 to −3.4) and younger TDM2 ages (1195–1223 Ma). The results show that the granodiorite and granite porphyry were formed from partial melting of different Mesoproterozoic basement rocks under varying degrees of crust–mantle interaction. Granite porphyry underwent well-recorded fractional crystallization. Compared to the Cu-forming granodiorite, the W-forming granite porphyry has a higher differentiation index, higher crystallization temperatures of zircon (average = 708 °C versus 631 °C), and lower oxygen fugacity (median ΔFMQ = –2.21 versus –1.77)

The Morphology of Cross-Beaks and BMP4 Gene Expression in Huiyang Bearded Chickens

Bird beaks are important for biological purposes such as food intake, removing parasites, and defining phenotypic attributes. Cross-beaks are a threat to poultry health and are harmful to productivity, wasting some units in the poultry industry. However, there is still limited research on subtypes of cross-beaks and the genetic basis of cross-beaks as well. Here, we described the subtypes of cross-beaks in terms of left or right and upper or lower jaw bones. We evaluated the impact of cross-beaks on craniofacial bones and figured out the relationship between bone morphogenetic protein 4 (BMP4) and the development of craniofacial bones in Huiyang bearded chickens. We identified five typical subtypes of cross-beaks by morphological assessment and X-ray scanning. We found that cross-beaks caused certain changes in the facial bone morphology, including changes to the length and width of the bone around the ocular area (p < 0.05). The relative expressions of BMP4 in lacrimal, mandible, premaxilla, frontal, and parietal bones were significantly higher in the severe cross-beak group, followed by that of the medium cross-beak group, weak cross-beak group, and control group (p < 0.05). Overall, we constructed a generally applicable method to classify cross-beaks in term of the angle. The skeleton around the ocular area was affected by the cross-beak. The expression levels of BMP4 in craniofacial bones may provide insight to potential role of BMP4 in the development of cross-beaks